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Dendritic cell-targeted vaccines — hope or hype?

Nature Reviews Immunology volume 14, pages 705–711 (2014)Cite this article

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Abstract

The development of an effective vaccine that elicits a strong and durable T cell response against intracellular pathogens and cancer is a challenge. One strategy to enhance the effectiveness of vaccination is by targeting dendritic cells (DCs). In this Opinion article, we discuss existing DC-targeting approaches that induce adaptive immunity. We highlight the crucial issues that need to be addressed to move the field forward and discuss whether targeting DCs could be better than current vaccine approaches.

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Figure 1: Antigen presentation and intracellular routing.

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Acknowledgements

W.K. and C.K. are members of the Deutsche Forschungsgemeinschaft Excellence Cluster ImmunoSensation in Bonn, Germany, and are supported by grant SFB704. W.K. is supported by the NRW-Rückkehrerprogramm of the German state of Northrhine-Westfalia. The authors thank G. Gasteiger, N. Garbi and their laboratory members for critically reading this manuscript.

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Authors and Affiliations

  1. Institute of Molecular Medicine, University of Bonn, 53105, Bonn, Germany

    Wolfgang Kastenmüller

  2. Institute of Experimental Immunology and the Department of General Practice and Family Medicine, University of Bonn, 53105, Bonn, Germany

    Kathrin Kastenmüller

  3. Institute of Experimental Immunology, University of Bonn, 53105, Bonn, Germany

    Christian Kurts

  4. Cellular Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, 20892–3005, Maryland, USA

    Robert A. Seder

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  2. Kathrin Kastenmüller
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Corresponding authors

Correspondence to Wolfgang Kastenmüller or Robert A. Seder.

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Supplementary information

Supplementary information S1 (table)

Targeted Vaccines (PDF 719 kb)

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Glossary

Adjuvants

Agents that are mixed with an antigen to increase the immune response to that antigen following immunization.

Conjugate vaccines

Vaccines that consist of an antigen and an adjuvant that are physically linked to allow for synchronous delivery of both components.

Cross-presentation

MHC class I antigen presentation of antigens that are not synthesized in the cytosol of a cell.

C-type lectins

Receptors that bind carbohydrates in a calcium-dependent manner. They can be classified on the basis of their signalling properties, which also influence the cellular routing of the internalized receptor and subsequent antigen presentation of the bound cargo.

Fcγ receptors

(FcγRs). Receptors that specifically bind to the crystallizable, non-antigen-binding part of IgG antibodies. Binding via FcγRs typically leads to internalization of the receptor and activation of the cell, thus enhancing phagocytosis and pathogen elimination.

Integrins

Transmembrane receptors that mediate attachments between cells or between cells and their surroundings — for example. the extracellular matrix or blood vessels.

Pattern recognition receptor

(PRR). A protein that is expressed by innate immune cells that detects molecules associated with microbial pathogens or cellular stress.

Toll-like receptor

(TLR). An evolutionarily conserved pattern recognition receptor. These molecules are located intracellularly and also at the cell surface of macrophages, dendritic cells, B cells and intestinal epithelial cells. Their natural ligands are conserved molecular patterns — known as pathogen-associated molecular patterns — which are found in bacteria, viruses and fungi.

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Kastenmüller, W., Kastenmüller, K., Kurts, C. et al. Dendritic cell-targeted vaccines — hope or hype?. Nat Rev Immunol 14, 705–711 (2014). https://doi.org/10.1038/nri3727

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